DESCRIPTION:

The goal of the talk will be to discuss the problem of drug tolerant persister cells in EGFR TKI treating lung cancer, and novel approaches to eradicate them. The key finding from our recent manuscript is that antibody drug conjugate therapy mediated cytotoxic drug delivery can delay relapse, but is unstable to eradicate these cells, likely due to their quiescent cell state. In contrast, chimeric antigen receptor (CAR) T cell therapy targeting the same epitope can result in tumor eradication when administered in the EGFR TKI minimal residual disease state. These findings provide proof of concept to develop even more potent and selective CAR-T cell therapies for eventual translation into the clinic.

LEARNING OBJECTIVES:

• Unique cell surface proteins such as TROP2 are enriched on drug tolerant persistent cells following EGFR targeted therapy, a concept that is likely generalizable to other targetable oncogenes as well.
• While antibody drug conjugate therapy may be one approach to intensify treatment during this minimal residual disease state, leveraging the immune system to eliminate these drug tolerant persister cells may have greater potential to promote long term durable responses and ultimately achieve cures in patients.